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triblock copolymer architecture is particularly useful for designing pressure sensitive adhesives (PSAs). The A‐ and B‐block usually comprised of glassy (minor, end component) and rubbery (major, central component), respectively. A‐block provide physical crosslinks and mechanical strength, while B‐block provide adhesion to the matrix. Commercial triblock copolymers adhesive properties could be improved by diluting entanglements in the central block. A‐block based on LA [267–269], γ‐methyl‐α‐methylene‐γ‐butyrolactone [270], and lactone acrylate [271] and B‐blocks based on β‐methyl‐δ‐valerolactone (βMδVL) [269] and ε‐decalactone (PDL) [268] sound promising from sustainability and degradability perspective. Copolymers based on LA with PDL or menthide‐based PSAs have also been reported because they can potentially degrade before or during the paper recycling process and simultaneously dilute entanglements and control viscosity, which are an essential criteria for their utility as PSAs [267]. An increase in the entanglement molar mass (M e) value was controlled by increasing the length of alkyl substituents in poly(n‐alkyl‐δ‐VL) without affecting the T g [272]. Recently, lactone sourced from cashewnut shell liquids (CNSLs)[273] seems to be promising sustainable approach being inexpensive, potentially degradable, and impart rubbery segment to affect rigidity of the block copolymer due to the presence of inherent long alkylene chain.
To impart surface hydrophilicity, porous scaffolds were successfully fabricated from copolymers of DXO, LLA, and ε‐CL through a solvent casting and particulate leaching technique, in which methanol was used to wet and swell the composite before leaching, thereby leading to an interconnected porous network. In the DSC thermograms of these copolymers, only a single T g located between corresponding copolymers was observed, indicating thereby a continuous amorphous phase due to the randomness of the copolymers [274]. In another approach, better hydrophilicity is achieved by surface functionalization of the porous resorbable scaffolds by covalent grafting [275].
4.6 DEGRADATION OF LACTIDE HOMO‐ AND COPOLYMERS
PLA and its copolymers especially when used for biological applications, besides requirement of optimization of mechanical properties by engineering at the molecular level, also demands a fast degradation polymer rate (less than usual reported time of a couple of months or years). A careful designing of polymer structure is required to optimize both these properties. To achieve a controllable degradation time of polymer demands exploration to satisfy various other desired parameters that are guided by end‐use application.
Hydrolysis of PLA under both alkaline and acidic conditions have been investigated. The presence of D‐lactoyl units reduces the hydrolysis rate [276]. The hydrolysis of copolymers of poly(LA‐co‐GA) was investigated at 37 and 60°C for 80 days. A three‐stage degradation was observed: during the first stage, the molar mass decreased rapidly with little mass loss; in the second stage, a severe mass loss was observed, and monomer formation was initiated; and in the third stage, via hydrolysis the oligomers were transformed to lactic acid and glycolic acid [277]. The GA units in the copolymers were hydrolyzed at a much faster rate than the LA units thus subsequently resulted in an increase in LA content in the remaining polymer.
Tacticity, nature, and length of sequencing in PLGAs found to affect the rate of degradation rate of PLGA. An alternating vs random PLGA exhibits a more gradual and constant degradation rate [90, 234, 236, 278]. Poly(LA‐co‐carbonate)s formed by polymerization of LA and 2‐methyl‐2‐benzyloxycarbonyl‐1,3‐trimethylene carbonate (MBC) followed by catalytic hydrogenation led to debenzylation of poly(LA‐co‐MBC)s to form poly(LA‐co‐MCC)s containing carboxylic acid groups. The degradation rates were significantly affected by their sequence distribution. The degradation rates significantly affected by LA–carbonate linkages in the main chains of copolymers with L–C/C–L linkages are more easily cleaved. The following descending trend of lactide–carbonate unit (L–C/C–L) > carbonate–carbonate unit (C–C) > lactide–lactide unit (L–L) of degradation is observed [279].
Hydrolysis of the triblock copolymer poly(LLA‐b‐DXO‐b‐LLA) of different compositions was studied in a buffered salt solution at 37°C and pH 7.4. The rate of degradation was influenced by the original molar mass of the sample, and the copolymer composition had no effect on the degradation [280]. During in vitro degradation carried out for 59 days for the elastic copolymers of DXO and LLA, both exhibited good retention of mechanical properties, with elongation at break 600–800% and elastic modulus 8–20 MPa.
The rate of degradation of PLA can be controlled by copolymerization with monomers such as CL, GA, DXO, α‐malate, glycine, HEMA, and ethylene glycol. Blending of PLLA with other polymers was also attempted [62]. Recently, covalent grafting of PLA to tune the in vitro degradation rate was reported. Grafting was performed with acrylamide, N‐vinylpyrrolidone, or acrylic acid. The in vitro rate of degradation was enhanced, and the grafted surface layer was found to be covalently attached to the surface [281].
Copolymers between LLA and TMC have been used to produce as multifilament fibers by high‐speed melt‐spinning process with an improved crystallinity [282]. The random copolymers of LLA and TMC (up to 18 mol%) enabled an overall longer service lifetime and a faster degradation kinetics than PLLA [283].
The rates of enzymatic hydrolysis (proteinase K) for branched PLLA (prepared from pentaerythritol with four branches and from polyglycerin with 22 branches) were found to be dependent on the average molar mass of the LLA block in the branched molecules, not on the overall molar mass of the samples [284].
The biodegradability of PLA has been extensively investigated in the literature [285–289]. PLLA and its copolymers degraded in the presence of different types of enzymes such as pronase, bromelain, Rhizopus delemar lipase, lipase from Rhizopus arrhizus, and proteinase K from Tritirachium album [285]. The enzymatic degradation by proteinase K was the subject of interest in several reports [276,286–289]. Reeve et al. [286] carried out the degradation of a series of PLA stereocopolymers by proteinase K and observed that the enzyme preferentially attacks L‐lactoyl units. The degradation of PLA stereocopolymers by proteinase K increased with a decrease in crystallinity and an increase in hydrophilicity of the polymers.
Recently, a method is devised to provide the real‐time assessment of degradability of biomedical polymers at physiological conditions [290]. Screening of degradability extent of series of aliphatic polyesters was determined by time‐dependent analysis of data obtained by polymer characterization and measuring the change in pH and released L‐lactate molecules using electrochemical sensors. Such advancements in analysis are highly desired to provide a degradation metrics for pristine polylactides or as copolymers.
Even the nature of initiator used in LA polymerization affect degradation characteristics. For example, non‐resorbable polyols such as xylitol and β‐cyclodextrin can assist the synthesis of star‐shaped polyester via ROP of natural xylitol with LLA. The mole fraction of xylitol used during the reaction was found to dictate the crystallinity of the polymer. Xylitol >6% resulted in amorphous polymer while less than 6% resulted in semicrystalline polymer. An increase in xylitol molar fraction concentration increased the rate of degradation of the polymer [291].
4.6.1 Drug Delivery from Lactide‐Based Copolymers
The successful utilization of polymer materials within the living body is highly dependent on the structural architecture and monomer unit distribution in the polymer. Nanoparticles with a hydrophobic surface (e.g., PLA and PLGA) are rapidly taken up by the cells of the reticuloendothelial systems (RES) [292]. Polymer particles with a hydrophilic surface can avoid this uptake to a greater extent, thereby prolonging the lifetime in the blood circulation, which may help in efficient delivery of the therapeutic agent. Self‐organizing block copolymers offers the possibility of entrapping a hydrophobic drug in the micelle core while the micelle’s hydrophilic shell confers water solubility. Intelligent drug delivery vehicles can be designed by utilizing shell forming polymers that exhibit stimuli‐responsive behavior. Block copolymers of DLA and NIPAAm are widely investigated